Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

Quintana, Dominic D.; Ren, Xuefang; Hu, Heng; Engler-Chiurazzi, Elizabeth B.; Rellick, Stephanie L.; Lewis, Sara E.; Povroznik, Jessica M.; Simpkins, James W.; Alvi, Mohammad Ali

doi:10.1007/s11011-018-0312-5

Cited by 7 publications

(6 citation statements)

References 32 publications

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“…Therefore, the association of LV dysfunction with subcortical structures, adjusted for early life factors, in this study supports this hypothesis. Hypoperfusion is associated with white matter damage near the subcortical nuclei in older adults [ 48 ], and animal models show particular vulnerability of the hippocampus and corpus callosum [ 49 , 50 ]. Nevertheless, although the effect of the cardiovascular system on the brain is physiologically plausible, this study cannot fully disentangle whether those cardiac–brain relationships that cannot be entirely attributed to early life factors are direct causal relationships or whether these have another common cause.…”

Section: Discussionmentioning

confidence: 99%

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors

Lapidaire

Clark

Fewtrell

et al. 2021

JCM

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People born preterm are at risk of developing both cardiac and brain abnormalities. We aimed to investigate whether cardiovascular physiology may directly affect brain structure in young adulthood and whether cardiac changes are associated with modifiable biomarkers. Forty-eight people born preterm, followed since birth, underwent cardiac MRI at age 25.1 ± 1.4 years and brain MRI at age 33.4 ± 1.0 years. Term born controls were recruited at both time points for comparison. Cardiac left and right ventricular stroke volume, left and right ventricular end diastolic volume and right ventricular ejection fraction were significantly different between preterm and term born controls and associated with subcortical brain volumes and fractional anisotropy in the corpus callosum in the preterm group. This suggests that cardiovascular abnormalities in young adults born preterm are associated with potentially adverse future brain health. Associations between left ventricular stroke volume indexed to body surface area and right putamen volumes, as well as left ventricular end diastolic length and left thalamus volumes, remained significant when adjusting for early life factors related to prematurity. Although no significant associations were found between modifiable biomarkers and cardiac physiology, this highlights that cardiovascular health interventions may also be important for brain health in preterm born adults.

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Section: Discussionmentioning

confidence: 99%

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors

Lapidaire

Clark

Fewtrell

et al. 2021

JCM

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“…Both common carotid arteries (CCAs) were exposed through a midline cervical incision, and an ameroid constrictor ring (cat. MC-0.50-55, Research Instruments SW, Escondido, CA, USA was placed around the right CCA following a published protocol [16,17]. A microcoil (cat.…”

Section: Implantation Of Ameroid Constrictor Ring and Microcoilmentioning

confidence: 99%

“…In the present study, we used a mouse model of cerebral hypoperfusion [16,17], by applying ameroid constrictor arterial stenosis (ACAS) surgery to induce chronic, progressive brain hypoperfusion and tested the effects of repeated administration of an IL-1β antibody on behavioral and neuropathology outcomes.…”

Section: Introductionmentioning

confidence: 99%

IL-1β Antibody Protects Brain from Neuropathology of Hypoperfusion

Quintana

Ren

et al. 2021

Cells

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Chronic brain hypoperfusion is the primary cause of vascular dementia and has been implicated in the development of white matter disease and lacunar infarcts. Cerebral hypoperfusion leads to a chronic state of brain inflammation with immune cell activation and production of pro-inflammatory cytokines, including IL-1β. In the present study, we induced chronic, progressive brain hypoperfusion in mice using ameroid constrictor, arterial stenosis (ACAS) surgery and tested the efficacy of an IL-1β antibody on the resulting brain damage. We observed that ACAS surgery causes a reduction in cerebral blood flow (CBF) of about 30% and grey and white matter damage in and around the hippocampus. The IL-1β antibody treatment did not significantly affect CBF but largely eliminated grey matter damage and reduced white matter damage caused by ACAS surgery. Over the course of hypoperfusion/injury, grip strength, coordination, and memory-related behavior were not significantly affected by ACAS surgery or antibody treatment. We conclude that antibody neutralization of IL-1β is protective from the brain damage caused by chronic, progressive brain hypoperfusion.

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“…Thus, while the model recapitulates a number of conditions observed in individuals with vascular cognitive impairment, it would be important to compare vascular and neuronal responses in a model that leads to a progressive reduction in CBF (carotid artery stenosis). To this end, the alternative ameroid constrictor model [80][81][82][83][84] should be considered. Nonetheless, the BCAS model provides insights on the impact transient ischemia (7-14 days) has on neurovascular function as well as on the adaptive and/or recovery processes of the brain when challenged with a transient rather than progressive insult.…”

Section: Limitations Of the Bcas Modelmentioning

confidence: 99%

Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment

et al. 2021

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Chronic hypoperfusion is a key contributor to cognitive decline and neurodegenerative conditions, but the cellular mechanisms remain ill-defined. Using a multidisciplinary approach, we sought to elucidate chronic hypoperfusion-evoked functional changes at the neurovascular unit. We used bilateral common carotid artery stenosis (BCAS), a well-established model of vascular cognitive impairment, combined with an ex vivo preparation that allows pressurization of parenchymal arterioles in a brain slice. Our results demonstrate that mild (~ 30%), chronic hypoperfusion significantly altered the functional integrity of the cortical neurovascular unit. Although pial cerebral perfusion recovered over time, parenchymal arterioles progressively lost tone, exhibiting significant reductions by day 28 post-surgery. We provide supportive evidence for reduced adenosine 1 receptor-mediated vasoconstriction as a potential mechanism in the adaptive response underlying the reduced baseline tone in parenchymal arterioles. In addition, we show that in response to the neuromodulator adenosine, the action potential frequency of cortical pyramidal neurons was significantly reduced in all groups. However, a significant decrease in adenosine-induced hyperpolarization was observed in BCAS 14 days. At the microvascular level, constriction-induced inhibition of pyramidal neurons was significantly compromised in BCAS mice. Collectively, these results suggest that BCAS uncouples vessel-to-neuron communication—vasculo-neuronal coupling—a potential early event in cognitive decline.

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Gradual common carotid artery occlusion as a novel model for cerebrovascular Hypoperfusion

Cited by 7 publications

References 32 publications

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors

The Preterm Heart-Brain Axis in Young Adulthood: The Impact of Birth History and Modifiable Risk Factors

IL-1β Antibody Protects Brain from Neuropathology of Hypoperfusion

Decreased parenchymal arteriolar tone uncouples vessel-to-neuronal communication in a mouse model of vascular cognitive impairment

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